Ryohei Okasato: Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Kuniyuki Kano: Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Ryoji Kise: Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Asuka Inoue: Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Shigetomo Fukuhara: Department of Molecular Pathophysiology, Institute of Advanced Medical Sciences, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
Junken Aoki: Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Lysophosphatidic acid (LPA) is a potential regulator of vascular formation derived from blood. In this study, we utilized zebrafish as a model organism to monitor the blood vessel formation in detail. Zebrafish mutant of ATX, an LPA-producing enzyme, had a defect in the caudal vein plexus (CVP). Pharmacological inhibition of ATX resulted in a fusion of the delicate vessels in the CVP to form large sac-like vessels. Mutant embryos of LPA receptor and downstream Gα showed the same phenotype. Administration of OMPT, a stable LPA-analog, induced rapid CVP constriction, which was attenuated significantly in the LPA mutant. We also found that blood flow-induced CVP formation was dependent on ATX. The present study demonstrated that the ATX-LPA axis acts cooperatively with blood flow and contributes to the formation and maintenance of the CVP by generating contractive force in endothelial cells.
